Cao Yu-Wen, Li Wen-Qin, Wan Guo-Xing, Li Yi-Xiao, Du Xiao-Ming, Li Yu-Cong, Li Feng
Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, 832000, China.
J Exp Clin Cancer Res. 2014 Nov 25;33(1):97. doi: 10.1186/s13046-014-0097-2.
SIRT1 expression and Notch1 signaling have been implicated in tumorigenesis in many cancers, but their association with survival in breast cancer has not been determined. The purpose of this study was to assess the possible prognostic value of SIRT1, N1IC, and Snail expression in breast cancer patients.
Immunohistochemistry was performed to examine the expression of SIRT1, N1IC, and Snail, and the combined expression of SIRT1 and N1IC, using tissue microarrays containing breast cancer tissue and matched adjacent normal breast tissue from 150 breast cancer patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of SIRT1, N1IC, Snail and combined SIRT1/N1IC expression, in addition to other clinicopathological factors, including grade, lymph node status, disease stage, and estrogen, progesterone, and human epidermal growth factor receptor 2 receptor status in breast carcinoma patients.
SIRT1, N1IC, and Snail were all found to be highly expressed and an inverse correlation between SIRT1 and N1IC in breast cancer tissue. The three markers significantly correlated with lymph node status. Patients with low SIRT1 expression exhibited shorter overall survival (OS) and disease-free survival (DFS), and patients with combined low expression of SIRT1 and high expression of N1IC had the worse OS and DFS. Univariate and multivariate survival analysis revealed that low expression of SIRT1 and SIRT1-low/N1IC-high expression were independent prognostic factors for poor survival.
These results suggest that low expression of SIRT1 or the combined low expression of SIRT1 and high expression of N1IC could be used as indicators of poor prognosis, and may represent novel therapeutic targets in breast cancer.
SIRT1表达和Notch1信号通路在多种癌症的肿瘤发生中发挥作用，但它们与乳腺癌患者生存率的关联尚未明确。本研究旨在评估SIRT1、N1IC和Snail表达在乳腺癌患者中的潜在预后价值。
利用包含150例乳腺癌患者的癌组织及配对的癌旁正常乳腺组织的组织芯片，采用免疫组织化学法检测SIRT1、N1IC和Snail的表达，以及SIRT1与N1IC的联合表达。采用Kaplan-Meier法进行生存分析。除了包括分级、淋巴结状态、疾病分期以及乳腺癌患者的雌激素、孕激素和人表皮生长因子受体2受体状态等其他临床病理因素外，还采用单因素和多因素分析来评估SIRT1、N1IC、Snail及SIRT1/N1IC联合表达的预后价值。
发现SIRT1、N1IC和Snail在乳腺癌组织中均高表达，且SIRT1与N1IC呈负相关。这三个标志物与淋巴结状态显著相关。SIRT1低表达的患者总生存期（OS）和无病生存期（DFS）较短，SIRT1低表达且N1IC高表达的患者OS和DFS更差。单因素和多因素生存分析显示，SIRT1低表达以及SIRT1低/N1IC高表达是生存不良的独立预后因素。
这些结果表明，SIRT1低表达或SIRT1低表达与N1IC高表达联合可作为预后不良的指标，可能代表乳腺癌新的治疗靶点。
